Ig enrichment strategies impact the LOQ. Observation of a unique MAb accurate mass in a serum matrix of patients undergoing therapy is accomplished among 1 g/dl of human endogenous circulating Igs. Depending on the MAb molecular mass, the LOQ can be an issue, as shown in this miRAMM example. When studying ECU, an IgG2/IgG4 hybrid MAb, different enrichment strategies were employed. (A) When Melon Gel enrichment was used, an ECU concentration of 5 μg/ml was not detectable. (B) Selective enrichment for IgG4 with an affinity matrix allowed for significant reduction of the endogenous Ig repertoire by removing all non-IgG4 Ig from the background and increased the analytical sensitivity of the assay by approximately 10-fold, with an increased signal-to-noise ratio.